Open Access Method

DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer

Ali Bashashati1, Gholamreza Haffari12, Jiarui Ding13, Gavin Ha14, Kenneth Lui1, Jamie Rosner1, David G Huntsman56, Carlos Caldas7, Samuel A Aparicio15 and Sohrab P Shah135*

  • * Corresponding author: Sohrab P Shah sshah@bccrc.ca

  • † Equal contributors

Author Affiliations

1 Department of Molecular Oncology, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada

2 Faculty of Information Technology, Monash University, Wellington Road, Clayton, VIC 3800, Australia

3 Department of Computer Science, University of British Columbia, 2366 Main Mall, Vancouver, BC, V6T 1Z4, Canada

4 Bioinformatics Training Program, University of British Columbia, 570 West 7th Avenue, Vancouver, BC, V5Z 4S6, Canada

5 Department of Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada

6 Centre for Translational and Applied Genomics, BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6 Canada

7 Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK

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Genome Biology 2012, 13:R124  doi:10.1186/gb-2012-13-12-r124

Published: 22 December 2012

Additional files

Additional file 1:

Supplementary text.

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Additional file 2:

Data analysis workflow.

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Additional file 3:

Ranked list of candidate driver genes using the Youn-Simon approach for the GBM2 dataset. rank: rank of the gene, hgnc_symbol: gene symbol, p.value: P value, p.adjust: adjusted P value using the Benjamini-Hochberg approach.

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Additional file 4:

Ranked list of candidate driver genes for the GBM2 dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

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Additional file 5:

Ranked list of candidate driver genes using the Youn-Simon approach for the TN2 dataset. rank: rank of the gene, hgnc_symbol: gene symbol, p.value: P value, p.adjust.BH: adjusted P value using the Benjamini- Hochberg approach.

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Additional file 6:

Ranked list of candidate driver genes for the TN2 dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 31KB Download file

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Additional file 7:

Ranked list of candidate driver genes using the Youn-Simon approach for the HGS2 dataset. rank: rank of the gene, hgnc_symbol: gene symbol, p.value: P value, p.adjust: adjusted P value using the Benjamini-Hochberg approach.

Format: XLS Size: 163KB Download file

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Additional file 8:

Ranked list of candidate driver genes for the HGS2 dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 166KB Download file

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Additional file 9:

Ranked list of candidate driver genes for the METABRIC dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

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Additional file 10:

Figure showing the SNVs/indels, homozygous deletion (HOMD), and high-level amplification (HLAMP) status across the patients for the top 190 candidate driver genes (ranked from top to bottom) for the METABRIC dataset. Genes with P values ≤ 0.05 are shown. Red blocks show HLAMPs and blue show HOMDs for each case.

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Additional file 11:

Ranked list of candidate driver genes for the HGS dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 208KB Download file

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Additional file 12:

Figure showing the SNVs/indels, homozygous deletion (HOMD), and high-level amplification (HLAMP) status across the patients for the top 144 candidate driver genes (ranked from top to bottom) for the HGS dataset. Genes with P values ≤ 0.05 are shown. Green blocks show SNVs or indels, red blocks show HLAMPs, and blue show HOMDs for each case.

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Additional file 13:

Ranked list of candidate driver genes for the TN dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 58KB Download file

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Additional file 14:

Figure showing the SNVs/indels, homozygous deletion (HOMD), and high-level amplification (HLAMP) status across the patients for the top 50 candidate driver genes (ranked from top to bottom) for the TN dataset. Genes with P values ≤ 0.05 are shown. Green blocks show SNVs or indels, red blocks show HLAMPs, and blue show HOMDs for each case.

Format: PDF Size: 39KB Download file

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Additional file 15:

Ranked list of candidate driver genes for the GBM dataset. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 49KB Download file

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Additional file 16:

Figure showing the SNVs/indels, homozygous deletion (HOMD), and high-level amplification (HLAMP) status across the patients for the top 49 candidate driver genes (ranked from top to bottom) for the GBM dataset. Genes with P values ≤0.05 are shown. Green blocks show SNVs or indels, red blocks show HLAMPs, and blue show HOMDs for each case.

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Additional file 17:

Circos plots showing outlying genes related to metabolic pathways for PNMT (A), NDUFC2 (B), and MTAP (C) and outlying genes related to oncogenic/tumor suppressor pathways for ERBB2 (D), PAK1 (E), and CDKN2A (F) genes.

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Additional file 18:

Frequency of aberrations versus the rank of significant genes (p ≤ 0.05) for the GBM (A), HGS (B), TN (C), and METABRIC (D) datasets.

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Additional file 19:

Node degree in the influence graph versus the rank of significant genes (p ≤ 0.05) for the GBM (A), HGS (B), TN (C), and METABRIC (D) datasets.

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Additional file 20:

DriverNet performance benchmarking on GBM, TN, HGS, and METABRIC datasets when copy number amplifications (AMP) and hemizygous deletions (HETDs) were included in addition to the high-level amplifications (HLAMP) and homozygous deletions (HOMDs). (A-D) Concordance with Cancer Gene Census for DriverNet, Frequency-based, and Fisher-based approaches as a function of the top N ranked genes (out of 200) for the GBM, TN, HGS, and METABRIC datasets, respectively. (E-H) Concordance with COSMIC database (cumulative distribution of mutation prevalence in the COSMIC database) for DriverNet, Frequency-based, and Fisher-based approaches as a function of the top N ranked genes (out of 200) for the GBM, TN, HGS, and METABRIC datasets, respectively.

Format: PDF Size: 223KB Download file

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Open Data

Additional file 21:

Ranked list of candidate driver genes for the METABRIC dataset when copy number amplifications and hemizygous deletions were included in addition to the mutations, high-level amplifications, and homozygous deletions. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 354KB Download file

Open Data

Additional file 22:

Ranked list of candidate driver genes for the HGS dataset when copy number amplifications and hemizygous deletions were included in addition to the mutations, high-level amplifications, and homozygous deletions. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 424KB Download file

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Additional file 23:

Ranked list of candidate driver genes for the TN dataset when copy number amplifications and hemizygous deletions were included in addition to the mutations, high-level amplifications, and homozygous deletions. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 152KB Download file

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Additional file 24:

Ranked list of candidate driver genes for the GBM dataset when copy number amplifications and hemizygous deletions were included in addition to the mutations, high-level amplifications, and homozygous deletions. rank: rank of the gene according to DriverNet, gene: gene symbol, gband: gene chromosome location and gene band, SNV.Indel: number of cases with SNV or indel in that specific gene, HLAMP: number of cases with copy number high-level amplifications, AMP: number of cases with copy number amplifications, HOMD: number of cases with copy number homozygous deletions, HETD: number of cases with copy number hemizygous deletions, covered events: the number of events (edges) connected to the gene on the left of the bipartite graph, node degree: the number of genes connected to the gene of interest in the influence graph, p.value: P value corrected for the multiple test using the Benjamini-Hochberg approach, CGC.status: Cancer Gene Census (CGC) membership status (1 = found in CGC, 0 = not in CGC), percentage.event: percentage of cases with genomic aberrations in the gene of interest, p.way: top pathways associated with outlying genes (posterior probability > 0.8); numbers in parentheses show the posterior probability.

Format: TXT Size: 154KB Download file

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